At 7 wk of age the normally domed tibial epiphysis was flattened and depressed in the knees of mutant animals, markedly reducing the distance between the growth plate and articular surface (Figure 7E and 7H, vertical bar). Articular cartilage was also thinner than in control animals, showed nearly complete absence of Safranin O staining, and was either acellular or beginning to fibrillate in many regions (Figure 7F and 7I). The few large Safranin O-stained cells still apparent in mutant articular regions appeared to correspond in position to rare LACZ-negative cells in adjacent sections, suggesting that Bmpr1a is required cell-autonomously in articular cartilage (Figure 7I and 7J, white arrowheads). By 9 mo, large areas of mutant knees were devoid of articular cells, and the bones of the femur and tibia appeared to rub directly against each other. Furthermore, the epiphysis of the tibia was extremely depressed, to the point that growth plate cartilage was almost exposed through the surface of the bone (Figure 7K, 7L, 7N, and 7O). In addition, mutants at 7 wk and 9 mo showed subchondral sclerosis, especially in the epiphysis of the femur (Figure 7E, 7H, 7K, and 7N, asterisks). While subchondral sclerosis is commonly seen in cases of osteoarthritis, it is unclear in this case whether the sclerosis is mainly a response of bone formation to compensate for decreased articular cartilage, or whether it is the effect of loss of Bmpr1a signaling in some LACZ-positive cells that are also observed in these regions (unpublished data).